Noncentrosomal microtubules and type II myosins potentiate epidermal cell adhesion and barrier formation

Sumigray, Kaelyn D.; Foote, Henry P.; Lechler, Terry

doi:10.1083/jcb.201206143

Cited by 63 publications

(105 citation statements)

References 39 publications

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“…It is known that microtubules regulate, and are regulated by, points of cell-cell contact (Chausovsky et al, 2000;Waterman-Storer et al, 2000;Yap and Manley, 2001;Ligon and Holzbaur, 2007), raising the possibility that microtubule network organisation is regulated at the supracellular or tissue level, as has recently been shown for the actomyosin system (Martin et al, 2009;Rauzi et al, 2010). However, there are a number of in vivo contexts where the ablation of microtubules was reported to have little influence on adherens junctions (Jankovics and Brunner, 2006;Brodu et al, 2010;Sumigray et al, 2012), indicating that the role of microtubules in tissue-shaping remains unclear.…”

Section: Introductionmentioning

confidence: 91%

Quantitative cell polarity imaging defines leader-to-follower transitions during collective migration and the key role of microtubule-dependent adherens junction formation

et al. 2014

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The directed migration of cell collectives drives the formation of complex organ systems. A characteristic feature of many migrating collectives is a 'tissue-scale' polarity, whereby 'leader' cells at the edge of the tissue guide trailing 'followers' that become assembled into polarised epithelial tissues en route. Here, we combine quantitative imaging and perturbation approaches to investigate epithelial cell state transitions during collective migration and organogenesis, using the zebrafish lateral line primordium as an in vivo model. A readout of three-dimensional cell polarity, based on centrosomal-nucleus axes, allows the transition from migrating leaders to assembled followers to be quantitatively resolved for the first time in vivo. Using live reporters and a novel fluorescent protein timer approach, we investigate changes in cell-cell adhesion underlying this transition by monitoring cadherin receptor localisation and stability. This reveals that while cadherin 2 is expressed across the entire tissue, functional apical junctions are first assembled in the transition zone and become progressively more stable across the leader-follower axis of the tissue. Perturbation experiments demonstrate that the formation of these apical adherens junctions requires dynamic microtubules. However, once stabilised, adherens junction maintenance is microtubule independent. Combined, these data identify a mechanism for regulating leader-to-follower transitions within migrating collectives, based on the relocation and stabilisation of cadherins, and reveal a key role for dynamic microtubules in this process.

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Section: Introductionmentioning

confidence: 91%

Quantitative cell polarity imaging defines leader-to-follower transitions during collective migration and the key role of microtubule-dependent adherens junction formation

et al. 2014

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“…These microtubules allow the transport machinery to deliver cilial regulatory proteins, and they promote cadherin clustering to maintain cell-cell junctions through the plus-end-binding protein CLIP170, and recruit myosin II for mechanical integrity at tight junctions (Bellett et al, 2009;Stehbens et al, 2006;Sumigray et al, 2012). However, the majority of the microtubules in epithelial cells are non-centrosomal and are aligned along the apical-basal axis, with their plus-ends orientated towards the basolateral membrane (Lüders and Stearns, 2007).…”

Section: Integrin-dependent Microtubule Dynamics Control Apical-basalmentioning

confidence: 99%

Integrins and epithelial cell polarity

Lee

Streuli

2014

Journal of Cell Science

126

117

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Cell polarity is characterised by differences in structure, composition and function between at least two poles of a cell. In epithelial cells, these spatial differences allow for the formation of defined apical and basal membranes. It has been increasingly recognised that cell-matrix interactions and integrins play an essential role in creating epithelial cell polarity, although key gaps in our knowledge remain. This Commentary will discuss the mounting evidence for the role of integrins in polarising epithelial cells. We build a model in which both inside-out signals to polarise basement membrane assembly at the basal surface, and outside-in signals to control microtubule apical-basal orientation and vesicular trafficking are required for establishing and maintaining the orientation of epithelial cell polarity. Finally, we discuss the relevance of the basal integrin polarity axis to cancer.

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“…We focused on adherens junctions because they are important for elongation (Costa et al, 1998;Pasti and Labouesse, 2014) and prior work has suggested a functional link between microtubules and adherens junctions (Stehbens et al, 2006;Meng et al, 2008;Bellett et al, 2009;Huang et al, 2011;Sumigray et al, 2012;Revenu et al, 2014). Examination of E-cadherin/HMR-1::GFP (Achilleos et al, 2010) revealed fragmentation of the cadherin-based junctional complex in 38% of noca-1(RNAi) and 66% of spas OE embryos (Fig.…”

Section: Epidermal Microtubules Promote E-cadherin Clustering and Turmentioning

confidence: 99%

“…This result is also consistent with the observation that MLC-4 (DD) is unable to rescue let-502(sb118ts) mutants, suggesting that MLC-4 is not the only target of LET-502 (Gally et al, 2009). In cell culture, perturbing microtubules impacts myosin II accumulation at cell-cell contacts (Stehbens et al, 2006;Sumigray et al, 2012), prompting us to examine MLC-4::GFP distribution in spas OE embryos (Gally et al, 2009). However, microtubule degradation had no apparent effect on MLC-4::GFP localization, and it was not enriched at junctions (Fig.…”

Section: Perturbation Of Epidermal Microtubules Leads To Mild Elongatmentioning

confidence: 99%

Non-centrosomal epidermal microtubules act in parallel to LET-502/ROCK to promote C. elegans elongation

Quintin¹,

Wang²,

Pontabry³

et al. 2016

Journal of Cell Science

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There was an error in Development (2016Development ( ) 143, 160-173 (doi: 10.1242).The first name of the second author was spelled incorrectly. The online version has now been corrected. The authors apologise to readers for this mistake. C. elegans embryonic elongation is a morphogenetic event driven by actomyosin contractility and muscle-induced tension transmitted through hemidesmosomes. A role for the microtubule cytoskeleton has also been proposed, but its contribution remains poorly characterized. Here, we investigate the organization of the noncentrosomal microtubule arrays present in the epidermis and assess their function in elongation. We show that the microtubule regulators γ-tubulin and NOCA-1 are recruited to hemidesmosomes and adherens junctions early in elongation. Several parallel approaches suggest that microtubule nucleation occurs from these sites. Disrupting the epidermal microtubule array by overexpressing the microtubulesevering protein Spastin or by inhibiting the C. elegans ninein homolog NOCA-1 in the epidermis mildly affected elongation. However, microtubules were essential for elongation when hemidesmosomes or the activity of the Rho kinase LET-502/ROCK were partially compromised. Imaging of junctional components and genetic analyses suggest that epidermal microtubules function together with Rho kinase to promote the transport of E-cadherin to adherens junctions and myotactin to hemidesmosomes. Our results indicate that the role of LET-502 in junctional remodeling is likely to be independent of its established function as a myosin II activator, but requires a microtubule-dependent pathway involving the syntaxin SYX-5. Hence, we propose that non-centrosomal microtubules organized by epidermal junctions contribute to elongation by transporting junction remodeling factors, rather than having a mechanical role.

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Noncentrosomal microtubules and type II myosins potentiate epidermal cell adhesion and barrier formation

Abstract: Noncentrosomal microtubules recruit myosin II to the cell cortex in order to engage adherens junctions and increase tight junction formation, resulting in an increase in mechanical integrity of cell sheets.

Cited by 63 publications

References 39 publications

Quantitative cell polarity imaging defines leader-to-follower transitions during collective migration and the key role of microtubule-dependent adherens junction formation

Quantitative cell polarity imaging defines leader-to-follower transitions during collective migration and the key role of microtubule-dependent adherens junction formation

Integrins and epithelial cell polarity

Non-centrosomal epidermal microtubules act in parallel to LET-502/ROCK to promote C. elegans elongation

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